The proposed research involves the study of inhibitors, both synthetic and natural, of the tRNA methyltransferases. The natural inhibitory systems we are studying are a competing enzyme, glycine methyltransferase, found in normal adult liver, kidney and pancreas but absent from foetal and tumor tissue; and a competing enzyme system, catechol-O-methyltransferase, which is altered in normal versus ovariectomized uterus. We are studying the effect of synthetic analogs of S-adenosylhomocysteine as inhibitors of methylation both in vitro and in vivo. BIBLIOGRAPHIC REFERENCES: Kerr, Sylvia J., "Interaction of Mammalian tRNA Methyltransferases with Heterologous and Homologous tRNA", Advances in Enzyme Regulation, 13, 379-390 (1975). Trewyn, R.W., and Kerr, Sylvia J., "Modulation of tRNA Modification in Cultured Cells by Extrinsic Agents", Federation Proceedings, 35, 1694 abs. (1976).